title: Efficacy studies of influenza vaccines: effect of end points used and characteristics of vaccine failures.
abstract: BACKGROUND
  End points used to detect influenza in vaccine efficacy trials have varied. Both the inactivated and live attenuated influenza vaccines are efficacious; however, failure to protect occurs.
  
  
  METHODS
  We compared characteristics of influenza A (H3N2) and B cases from 3 years of a comparative placebo-controlled trial of inactivated and live attenuated vaccines, and we evaluated the laboratory end points used to determine efficacy.
  
  
  RESULTS
  Although illness duration and reported symptoms did not differ by intervention, subjects with influenza in the inactivated vaccine group were less likely than those in the placebo group to report medically attended illnesses. All influenza type A (H3N2) and B cases isolated in cell culture were also identified by real-time polymerase chain reaction (rtPCR). However, only 69% of type A (H3N2) cases identified by rtPCR also were isolated in cell culture. Isolation frequency was lowest among live attenuated vaccine failures, a reflection of lower specimen viral loads. Among cases of rtPCR identified influenza A (H3N2), 90% of placebo and 87% of live attenuated vaccine recipients but only 23% of inactivated vaccine recipients demonstrated serologic confirmation of infection.
  
  
  CONCLUSIONS
  In influenza vaccine efficacy studies, virus identification using rtPCR is the ideal end point. Isolation in cell culture will miss cases, and a serologic end point alone will overestimate inactivated vaccine efficacy.
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
authors.forename: Joshua G
authors.initials: JG
authors.lastname: Petrie
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Ohmit
authors.forename: Emileigh
authors.initials: E
authors.lastname: Johnson
authors.forename: Rachel T
authors.initials: RT
authors.lastname: Cross
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Monto
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D015415:Biomarkers; D035843:Biomedical Research / Q000379:methods*; D018849:Controlled Clinical Trials as Topic / Q000379:methods*; D005260:Female; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014613:Vaccines, Attenuated / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated